The adrenal steroid corticosterone is known to enhance glutamate neurotoxicity in the hippocampus. Corticosteroids are proposed to contribute to neurotoxic events such as hypoxia, ischemia and hypoglycemia by potentiating the activity of glutamate in the synapse, which ultimately results in the activation of nitric oxide synthase(NOS). However, in addition to potentiating the action of glutamate, corticosteroids may also modulate these events by regulating the expression of NOS isoforms. Accordingly, the objective of this proposal are to examine corticosteroid regulation of NOS isoforms in experimental paradigms which produce stress-induced neuronal atrophy in the hippocampus. Changes in the expression of NOS isoforms in the hippocampus will be examined by in situ hybridization histochemisty. The ability of inhibitors of NOS activity to attenuate corticosteroid mediated neuronal atrophy will also be evaluated. These studies will allow for a better understanding of the underlying molecular mechanisms through which corticosteroids produce neuronal atrophy during stress. In addition, these results could contribute to the development of therapeutic interventions applicable during such pathological insults as hypoxia, ishemia and hypoglycemia.